Postprandial Hyperinsulinemia Research Articles

Insulin Response to Oral Glucose and Cardiometabolic Disease: A Mendelian Randomization Study to Assess Potential Causality.

Mendelian randomization (MR) suggests that postprandial hyperinsulinemia (unadjusted for plasma glucose) increases BMI, but its impact on cardiometabolic disease, a leading cause for mortality and morbidity in people with obesity, is not established. Fat distribution i.e., increased centripetal and/or reduced femoro-gluteal adiposity, is causally associated with and better predicts cardiometabolic disease than BMI. We therefore undertook bidirectional MR to assess the effect of corrected insulin response (CIR) (insulin 30 min after a glucose challenge adjusted for plasma glucose) on BMI, waist-to-hip ratio (WHR), leg fat, type 2 diabetes (T2D), triglyceride (TG), HDL, liver fat, hypertension (HTN), and coronary artery disease (CAD) in people of European descent. Inverse variance-weighted MR suggests a potential causal association between increased CIR and increased BMI (b = 0.048 ± 0.02, P = 0.03), increased leg fat (b = 0.029 ± 0.012, P = 0.01), reduced T2D (b = -0.73 ± 0.15, P = 6 × 10-7, odds ratio [OR] 0.48 [95% CI 0.36-0.64]), reduced TG (b = -0.07 ± 0.02, P = 0.003), and increased HDL (b = 0.04 ± 0.01, P = 0.006) with some evidence of horizontal pleiotropy. CIR had neutral effects on WHR (b = 0.009 ± 0.02, P = 0.69), liver fat (b = -0.08 ± 0.04, P = 0.06), HTN (b = -0.001 ± 0.004, P = 0.7, OR 1.00 [95% CI 0.99-1.01]), and CAD (b = -0.002 ± 0.002, P = 0.48, OR 0.99 [95% CI 0.81-1.21]). T2D decreased CIR (b -0.22 ± 0.04, P = 1.3 × 10-7), with no evidence that BMI, TG, HDL, liver fat, HTN, and CAD modulate CIR. In conclusion, we did not find evidence that increased CIR increases cardiometabolic disease. It might increase BMI with favorable fat distribution, reduce T2D, and improve lipids.

A Pilot Study to Assess Glucose, Insulin, and Incretin Responses Following Novel High Resistant Starch Rice Ingestion in Healthy Men.

IntroductionA newly developed resistant starch (RS) rice line with double mutation of starch synthase IIIa and branching enzyme IIb (ss3a/be2b) exhibits a tenfold greater percentage RS value than the wild-type rice line. Currently, the effects of cooked rice with such high RS content on secretion and action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are unclear. Therefore, we conducted a pilot study to assess postprandial responses of GLP-1 and GIP along with glucose and insulin and also gastric emptying after ingestion of the high-RS cooked rice with ss3a/be2b in healthy subjects.MethodsIn a non-randomized crossover design, five healthy men ingested two test foods, control (low-RS) and high-RS cooked rice, with at least 1-week washout period between testing days. Plasma glucose, serum insulin, plasma total GLP-1, plasma total GIP, and also gastric emptying rate were measured after ingestion of each test food, and the incremental area under the curves (iAUC) was calculated for each biochemical parameter using the values from 0 to 180 min after ingestion.ResultsThe high-RS cooked rice ingestion tended to reduce iAUC-glucose (p = 0.06) and significantly reduced iAUC-insulin (p < 0.01) and iAUC-GLP-1 (p < 0.05) but not iAUC-GIP (p = 0.21) relative to control cooked rice ingestion. In addition, the high-RS cooked rice ingestion did not affect gastric emptying.ConclusionsThe present results indicate that the suppressive effects of the high-RS cooked rice ingestion on postprandial responses of glucose and insulin may be provided through attenuation in GLP-1 secretion along with its low digestibility into glucose. We suggest that the high-RS rice with ss3a/be2b may serve as a better carbohydrate source and also as a novel functional food for dietary interventions to improve postprandial hyperglycemia and hyperinsulinemia without both enhancing GLP-1 secretion and affecting gastric emptying in patients with diabetes.

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

Beyond Thermal Sensation: Roles of Transient Receptor Potential Vanilloid Subfamily Member 1 and Spicy Food in Cardiometabolic Diseases

УДОСКОНАЛЕННЯ ТЕХНОЛОГІЇ СОУСІВ З ВИКОРИСТАННЯ ОВОЧЕВО-ЯГІДНОЇ СИРОВИНИ

In developed areas, with the accelerated pace of life, the pressure of work is increasing, and the number of sub-healthy people is increasing. People begin to pay attention to health care. With the enhancement of people’s awareness of health care and the pursuit of nutritious food, chia seeds have gradually become a hot spot in the field of food research. Chia seeds have a long history of being edible, and they have been paid attention to and utilized in China in recent years. The active ingredients of chia seeds mainly include fatty acids, phenolic flavonoids, protein, dietary fiber, vitamins and minerals, which have anti-oxidation, blood lipid regulation, blood pressure regulation, blood sugar regulation, creatine kinase reduction, anti-inflammatory disinfection and other physiological functions effect. In this study, cherries and purple cabbage were used to improve the sauce technology. Cherries and purple cabbage were used as the main raw materials, and chia seeds and other auxiliary materials were added to it, and the optimal formula of fruit and vegetable sauce was studied from the aspect of formula. By designing a single factor test and an orthogonal test, the comprehensive sensory evaluation of different raw and auxiliary materials on fruit and vegetable sauces was studied, and the best formula for making fruit and vegetable sauces was 160 grams of cherries, 110 grams of purple cabbage, 6 grams of chia seeds, 60 grams of 1.5 grams of white sugar, 1.5 grams of pectin, and 7 grams of lemon juice. The fruit and vegetable sauce produced by this formula has moderate sweetness and sourness, good color, unique flavor, good spreadability and good stability. Among the main functional ingredients of the product, dietary fiber is the most abundant. Adequate intake of dietary fiber can reduce the postprandial blood sugar level of diabetic patients, and at the same time reduce the risk of postprandial hyperlipidemia, hyperinsulinemia and other chronic diseases. The shelf life is very important for food manufacturers and consumers. This study uses the classic constant temperature accelerated test method, and according to the ALST test (shelf life test), the shelf life of the fruit and vegetable sauce is 300d.

Blueberry effects on prediabetic nephropathy—a preclinical in vivo approach

Abstract Background Prediabetic Nephropathy (PreDN) therapeutic arsenal remains scarce. Blueberries (BB) display insulin sensitizing, lipid-lowering, antioxidant and anti-inflammatory effects. Therefore, we aimed to assess the putative benefits arising from BB supplementation in experimental PreDN. Methods BB polyphenol (PP) content was assessed by HPLC/PDA/ESI-MSn. Twenty-four male Wistar rats were divided in three groups (n = 8) for 24 weeks: Control group (Standard chow, Sd), 45% High-Fat (HF) diet-induced PreDN group and BJ-treated group (HF+BJ) [25 g/kg BW per day from week 16 onwards]. Glycemic/insulinemic/lipidic profiles were examined. Renal function was assessed by serum/urinary measures of creatinine, albumin, uric acid and glucose. Kidney histological characterization was performed by Periodic Acid-Shiff and Gomori’s green trichrome staining. Relative gene expression (RT-PCR) was also evaluated (KIM-1, NLRP3). Values are means ± S.E.M (ANOVA/post-hoc tests). This work was approved by the ORBEA of iCBR-FMUC (9/2018). Results HPLC/PDA/ESI-MSn analysis revealed that the main PP’s present in BB are malvidin derivatives, quercetin-O-hexoside and caffeic acid. HF animals displayed increased BW, glucose intolerance, postprandial hyperinsulinemia, elevated circulating LDL-c, hepatic/renal lipidosis, mild impairments in renal function and histological lesions resembling the stages I/II of PreDN. Apart from ameliorating prediabetic glucose intolerance, BJ supplementation elicited hepatic lipid accumulation and increased gene expression of renal inflammasome and KIM-1 without major improvements on renal function and/or histopathology. Conclusions Even though BB was able to ameliorate prediabetic glucose intolerance, the BB dosage employed herein (25 g/kg BW) elicited deleterious effects in the kidney only perceived at a sub-clinical level.

The impact of refined food processing on the kidney—preclinical evaluation

Abstract Background Purified diets combine refined ingredients that convey a precise nutritional load. At a preclinical level, these formulas are used to dissect the impact of each nutrient on a given phenotype, from excess [e.g. High Fat (HF) diet] to deficiency [e.g. Low Fat (LF) diet; a nutrient-matched control]. Yet, processing strategies deteriorate the health potential of cereal-based diets as reported in a panoply of diseased conditions. Herein, we aim to disclose the impact of refined ingredients in the kidney. Methods Twenty-four male Wistar rats were divided in three groups (n = 8) for 24 weeks: Control group (8.57 Kcal/fat), HF group (45% Kcal/fat) and the LF group (13% Kcal/fat). In vivo glycemic/insulinemic/lipidic profiles were assessed. Renal parameters evaluated were serum/urinary measures of uric acid/albumin/creatinine/glucose. Periodic Acid-Shiff and Gomori’s green trichrome staining were used to gauge kidney histology. Renal KIM-1/NLRP3 relative gene expression (RT-PCR) was also evaluated. Values are means ± S.E.M (ANOVA/post-hoc tests). This work was approved by the ORBEA of iCBR-FMUC (9/2018). Results HF-fed animals displayed a phenotype aligned with a prediabetic condition: glucose intolerance, postprandial hyperinsulinemia, hepatic/renal lipidosis, mild renal dysfunction and initial histological lesions. Surprisingly, LF-fed animals also displayed glucose intolerance and postprandial hyperinsulinemia paralleling an exacerbated renal injury phenotype: LF-fed animals displayed a decrease in creatinine clearance along with glycosuria (P &amp;lt; 0.05). Histological/gene expression markers collectively indicate kidney damage. Conclusions Our findings allude for prominent renal impairments arising from LF feeding. These results claim for a cautious selection of ‘control’ diets when kidney diseases are foreseen.

Association between sleep with C-reactive protein and insulin metabolism in adolescents

Objective To explore the relationship of sleep with C-reactive protein (CRP) abnormality and hyperinsulinemia in adolescents, and to provide reference for early prevention of metabolic disorders. Methods Based on the Chinese Metabolic Syndrome Cohort Study in Anhui Province, a total of 653 adolescents aged 12 to 19 were selected to examine the relationship between wakeup time, bedtime, sleep disordered breathing (SDB) and CRP abnormality as well as hyperinsulinemia. Results Later wakeup time (OR=1.68, 95%CI=1.03-2.75) was positively correlated with a higher risk of fasting hyperinsulinemia. Late bedtime (OR=1.96, 95%CI=1.29-2.99) was associated with 2 h postprandial hyperinsulinemia. Among those with high CRP concentration, late wakeup time and late bedtime were positely associated with hyperinsulinemia than those with normal CRP concentration; and the correlation between SDB and hyperinsulinemia was observed. Conclusion Later wakeup and late bedtime may be risk factors for hyperinsulinemia in adolescents. High concentrations of CRP may further increase the risk of hyperinsulinemia, a condition associated with sleep problems.Teenagers should get up and go to bed as early as possible.

Age-dependent transition from islet insulin hypersecretion to hyposecretion in mice with the long QT-syndrome loss-of-function mutation Kcnq1-A340V

Loss-of-function (LoF) mutations in KCNQ1, encoding the voltage-gated K+ channel Kv7.1, lead to long QT syndrome 1 (LQT1). LQT1 patients also present with post-prandial hyperinsulinemia and hypoglycaemia. In contrast, KCNQ1 polymorphisms are associated with diabetes, and LQTS patients have a higher prevalence of diabetes. We developed a mouse model with a LoF Kcnq1 mutation using CRISPR-Cas9 and hypothesized that this mouse model would display QT prolongation, increased glucose-stimulated insulin secretion and allow for interrogation of Kv7.1 function in islets. Mice were characterized by electrocardiography and oral glucose tolerance tests. Ex vivo, islet glucose-induced insulin release was measured, and beta-cell area quantified by immunohistochemistry. Homozygous mice had QT prolongation. Ex vivo, glucose-stimulated insulin release was increased in islets from homozygous mice at 12–14 weeks, while beta-cell area was reduced. Non-fasting blood glucose levels were decreased at this age. In follow-up studies 8–10 weeks later, beta-cell area was similar in all groups, while glucose-stimulated insulin secretion was now reduced in islets from hetero- and homozygous mice. Non-fasting blood glucose levels had normalized. These data suggest that Kv7.1 dysfunction is involved in a transition from hyper- to hyposecretion of insulin, potentially explaining the association with both hypoglycemia and hyperglycemia in LQT1 patients.

Influence of dietary insulin scores on survival in patients with metastatic colorectal cancer (mCRC): Findings from CALGB (Alliance) 80405.

3568 Background: Diets inducing an elevated insulin response have been associated with increased recurrence and mortality in patients with non-metastatic colorectal cancer, but it remains unknown if postprandial hyperinsulinemia also affects progression and mortality in mCRC patients. The goal of this study was to assess the influence of dietary insulin load (DIL) and dietary insulin index (DII) on survival of mCRC patients. Methods: This was a prospective cohort study of 1,177 patients with previously untreated mCRC enrolled in a phase III trial of systemic chemotherapy plus biologics who reported dietary intake within one month after chemotherapy initiation. DIL was calculated as a function of food insulin index and the energy content of individual foods reported on a food frequency questionnaire. DII was calculated by dividing DIL by total energy intake. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). The primary statistical test was a test for trend, which was performed using the median value for each quintile of dietary insulin score as a continuous variable. Cox proportional hazards regression was used to adjust for potential confounders including assigned treatment arm, known prognostic factors, comorbidities, body mass index, and physical activity. Results: Higher DIL was significantly associated with worse OS (ptrend = 0.04); patients in the highest quintile survived 34.1 months, compared to 27.7 months in the lowest quintile (Cox hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.99 - 1.51). Higher DII was non-significantly associated with worse OS (HR 1.18, 95% CI 0.94 - 1.48, ptrend = 0.09). There was no significant association between dietary insulin scores and PFS. The influence of dietary insulin scores on survival did not differ significantly by various molecular markers involved in the insulin signaling pathway, including C-peptide, adiponectin, IGF-1, IGFBP-3, and IGFBP-7. Higher dietary insulin scores were significantly associated with greater risk of any TRAE. Those with a DIL greater than the median had a 75.4% rate of any TRAE, compared to 70.8% in those with a DIL less than or equal to the median (HR 1.19, 95% CI 1.03 - 1.38, p=0.02); the most significant associations were with neutropenia (HR 1.30, 95% CI 1.05 - 1.61, p=0.01) and diarrhea (HR 1.43, 95% CI 1.00 - 2.06, p=0.05). Conclusions: Higher DIL was significantly associated with worse OS, and both higher DIL and DII were significantly associated with increased TRAEs, in patients with previously untreated mCRC. These findings may inform future dietary recommendations for patients with mCRC. Further investigation into the molecular mechanisms underlying these associations is warranted. Clinical trial information: NCT00265850.

Tissue-Specific Splicing and Dietary Interaction of a Mutant As160 Allele Determine Muscle Metabolic Fitness in Rodents.

Ethnic groups are physiologically and genetically adapted to their diets. Inuit bear a frequent AS160R684X mutation that causes type 2 diabetes. Whether this mutation evolutionarily confers adaptation in Inuit and how it causes metabolic disorders upon dietary changes are unknown due to limitations in human studies. Here, we develop a genetically modified rat model bearing an orthologous AS160R693X mutation, which mimics human patients exhibiting postprandial hyperglycemia and hyperinsulinemia. Importantly, a sugar-rich diet aggravates metabolic abnormalities in AS160R693X rats. The AS160R693X mutation diminishes a dominant long-variant AS160 without affecting a minor short-variant AS160 in skeletal muscle, which suppresses muscle glucose utilization but induces fatty acid oxidation. This fuel switch suggests a possible adaptation in Inuit who traditionally had lipid-rich hypoglycemic diets. Finally, induction of the short-variant AS160 restores glucose utilization in rat myocytes and a mouse model. Our findings have implications for development of precision treatments for patients bearing the AS160R684X mutation.

A Potential Role for Endogenous Glucagon in Preventing Post-Bariatric Hypoglycemia.

Obesity and obesity-related diseases are major public health concerns that have been exponentially growing in the last decades. Bariatric surgery is an effective long-term treatment to achieve weight loss and obesity comorbidity remission. Post-bariatric hypoglycemia (PBH) is a late complication of bariatric surgery most commonly reported after Roux-en-Y gastric bypass (RYGB). PBH is the end result of postprandial hyperinsulinemia but additional endocrine mechanisms involved are still under debate. Our aim was to characterize entero-pancreatic hormone dynamics associated with postprandial hypoglycemia after RYGB. Individuals previously submitted to RYGB (N=23) in a single tertiary hospital presenting PBH symptoms (Sym, n=14) and asymptomatic weight-matched controls (Asy, n=9) were enrolled. Participants underwent a mixed-meal tolerance test (MMTT) to assess glucose, total amino acids (total AA), insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and neurotensin (NT). We found that hypoglycemia during the MMTT was equally frequent in Sym and Asy groups (p=1.000). Re-grouped according to glucose nadir during the MMTT (Hypo n=11 vs NoHypo n=12; nadir <3.05 mmol/l vs ≥3.05 mmol/l), subjects presented no differences in anthropometric (BMI: p=0.527) or metabolic features (HbA1c: p=0.358), yet distinct meal-elicited hormone dynamics were identified. Postprandial glucose excursion and peak glucose levels were similar (p>0.05), despite distinct late glycemic outcomes (t=60 min and t=90 min: p<0.01), with overall greater glycemic variability in Hypo group (minimum-to-maximum glucose ratio: p<0.001). Hypo group meal-triggered hormone profile was characterized by lower early glucagon (t=15 min: p<0.01) and higher insulin (t=30 min: p<0.05, t=45 min: p<0.001), C-peptide (t=30 min: p<0.01, t=45 min: p<0.001, t=60 min: p<0.05), and GLP-1 (t=45 min: p<0.05) levels. Hyperinsulinemia was an independent risk factor for hypoglycemia (p<0.05). After adjusting for hyperinsulinemia, early glucagon correlated with glycemic nadir (p<0.01), and prevented postprandial hypoglycemia (p<0.05). A higher insulin to glucagon balance in Hypo was observed (p<0.05). No differences were observed in total AA, GIP or NT excursions (p>0.05). In sum, after RYGB, postprandial hyperinsulinemia is key in triggering PBH, but a parallel and earlier rise in endogenous glucagon might sustain the inter-individual variability in glycemic outcome beyond the effect of hyperinsulinism, advocating a potential pivotal role for glucagon in preventing hyperinsulinemic hypoglycemia.

Decreased arterial distensibility and postmeal hyperinsulinemia in young Japanese women with family history of diabetes

IntroductionTo assess vascular function and characterize insulin secretion using a physiological approach in Japanese women with family history of type 2 diabetes (FHD).Research design and methodsStandardized mixed-meal tests were performed...

Does food insulin index in the context of mixed meals affect postprandial metabolic responses and appetite in obese adolescents with insulin resistance? A randomised cross-over trial.

The food insulin index (II) is a novel classification to rank foods based on their physiological insulin demand relative to an isoenergetic reference food and may be a valid predictor of postprandial insulin responses and appetite. The present study aimed to compare the postprandial metabolic responses and appetite sensations to two macronutrient- and glycaemic index-matched meals with either high or low II in obese adolescents with insulin resistance (IR). A randomised, single-blind and cross-over trial included fifteen obese adolescents aged 12-18 years with IR. All participants were provided with two different breakfasts: low glycaemic index, low insulin index (LGI-LII) and low glycaemic index, high insulin index (LGI-HII), with a 1-week washout period between meals. At time 0 (just before breakfast), 15, 30, 45, 60, 90, 120, 180 and 240 min after the meal, serum glucose, insulin and C-peptide levels and appetite scores were measured. At the end of 4 h, participants were served ad libitum lunch. Early (0-30 min), late (45-240 min) and total (0-240 min) postprandial insulin responses were lowered by 56·1, 34·6 and 35·6 % after the LGI-LII meal v. LGI-HII meal (P < 0·05). The feeling of hunger was also decreased by 25·8 and 27·5 % after the LGI-LII meal v. LGI-HII meal during the late and total responses (P < 0·05). The calculation II of meals or diets may be a useful dietary approach to reduce postprandial hyperinsulinaemia and the perceived hunger in obese adolescents with IR.

Sex, puberty, and ethnicity have a strong influence on growth and metabolic comorbidities in children and adolescents with obesity: Report on 1300 patients (the Madrid Cohort).

The capacity to correctly assess insulin resistance and its role in further obesity-associated metabolic derangement in children is under debate, and its determinants remain largely unknown. We investigated the association of the insulin secretion profile with other metabolic derangements and anthropometric features in children and adolescents with obesity, exploring the role of ethnicity. Growth and metabolic features, including fasting insulin levels and insulin secretory profile in an oral glucose tolerance test (OGTT), were analyzed according to ethnicity in 1300 patients with obesity (75.8% Caucasians/19.0% Latinos). Height and bone age were influenced by sex, ethnicity, and insulinemia. Latino patients had higher insulin (P<.001), but similar glycemia both prepubertally and postpubertally, compared with Caucasians. Type 2 diabetes was uncommon (0.1%). Impaired glucose tolerance was associated to higher age, BMI, uric acid, and triglyceride levels (all P<.05), as was fasting hyperinsulinism. Impaired fasting glucose or HbA1c 5.7% to 6.4% showed no association with further metabolic derangement. A delayed insulin peak in the OGTT was associated to more severe metabolic disturbances. Obesity-associated hyperglycemia is unusual in our environment whereas fasting and late postprandial hyperinsulinemia are highly prevalent, with this being influenced by race and closely related with lipid metabolism impairment.

How does exercise support dietary approaches to weight loss and better health?

The rapid global rise of obesity incurs a heavy personal and healthcare burden due to obesity-associated morbidities and shortening of life. The purpose of this review is to provide evidence-based strategies for prevention, reversal, and mitigation of obesity and its sequelae. To that end, this review highlights the features of human physiology that favor fat accretion and interfere with fat loss. Strategies for prevention of obesity include understanding the basis for the strong motivating properties of palatable food, for human inability to consciously detect calories eaten or calories expended through exercise, for metabolic and hormonal adaptations to negative energy balance that drive weight regain, and for evolutionary natural selection which likely led to high human capacity for fat storage. Reversal of obesity is difficult primarily due to metabolic, hormonal, and behavioral reactions to body fat loss. Reduced resting metabolic rate presents a physiological challenge whether the weight loss is achieved through dietary restriction or energy expenditure of exercise. Increased insulin sensitivity after body fat loss drives resynthesis of storage substrates including triglycerides in the adipose tissue, muscle glycogen, and proteins, thus contributing to weight regain. Reduced basal plasma leptin concentration elicits a strong hunger drive. Mitigation of obesity-associated morbidities involves adding exercise energy expenditure to deliberate control of the quantity of food eaten, reducing postprandial hyperinsulinemia by lowering the carbohydrate load of the diet, and exercising after, rather than before, the meals to facilitate improved glucose tolerance.

Insulin Stimulates GLUT4 Trafficking to the Syncytiotrophoblast Basal Plasma Membrane in the Human Placenta.

Placental transport capacity influences fetal glucose supply. The syncytiotrophoblast is the transporting epithelium in the human placenta, expressing glucose transporters (GLUTs) and insulin receptors (IRs) in its maternal-facing microvillous plasma membrane (MVM) and fetal-facing basal plasma membrane (BM). The objectives of this study were to (i) determine the expression of the insulin-sensitive GLUT4 glucose transporter and IR in the syncytiotrophoblast plasma membranes across gestation in normal pregnancy and in pregnancies complicated by maternal obesity, and (ii) assess the effect of insulin on GLUT4 plasma membrane trafficking in human placental explants. Placental tissue was collected across gestation from women with normal body mass index (BMI) and mothers with obesity with appropriate for gestational age and macrosomic infants. MVM and BM were isolated. Protein expression of GLUT4, GLUT1, and IR were determined by western blot. GLUT4 was exclusively expressed in the BM, and IR was predominantly expressed in the MVM, with increasing expression across gestation. BM GLUT1 expression was increased and BM GLUT4 expression was decreased in women with obesity delivering macrosomic babies. In placental villous explants, incubation with insulin stimulated Akt (S473) phosphorylation (+76%, P = 0.0003, n = 13) independent of maternal BMI and increased BM GLUT4 protein expression (+77%, P = 0.0013, n = 7) in placentas from lean women but not women with obesity. We propose that maternal insulin stimulates placental glucose transport by promoting GLUT4 trafficking to the BM, which may enhance glucose transfer to the fetus in response to postprandial hyperinsulinemia in women with normal BMI.

The influence of the prediabetes phenotype on the efficacy of lifestyle interventions to improve glycemia, insulin resistance and postprandial hyperinsulinaemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Role of vagal activation in postprandial glucose metabolism after gastric bypass in individuals with and without hypoglycaemia.

Patients who have undergone gastric bypass surgery (GB) have enhanced postprandial hyperinsulinaemia and a greater incretin effect is apparent. In the present study, we sought to determine the effect of vagal activation, a neural component of the enteroinsular axis, on postprandial glucose metabolism in patients with and without hypoglycaemia after GB. Seven patients with documented post-GB hypoglycaemia, seven asymptomatic patients without hypoglycaemia post-GB, and 10 weight-matched non-surgical controls with normal glucose tolerance were recruited. Blood glucose, and islet hormone and incretin secretion were compared during mixed meal tolerance tests (MMTs) with and without prior sham-feeding on two separate days. Sham feeding preceding the MMT caused a more rapid increase in prandial blood glucose levels but lowered overall glycaemia in all three groups (P < 0.05). Sham feeding had a similar effect to increase early (P < 0.05), but not overall, meal-induced insulin secretion in the three groups. Prandial glucagon concentrations were significantly greater in the GB groups, and sham feeding accentuated this response (P < 0.05). The effect of vagal activation on prandial glucose and islet-cell function is preserved in patients who have undergone GB, in those both with and without hypoglycaemia.

IMPACT OF DECREASED INSULIN RESISTANCE BY EZETIMIBE ON POSTPRANDIAL LIPID PROFILES AND ENDOTHELIAL FUNCTIONS IN OBESE, NON-DIABETIC METABOLIC SYNDROME PATIENTS WITH CORONARY ARTERY DISEASE

Little is known regarding the relationship between insulin resistance and lipid dysmetabolism after consuming a meal. We aimed to assess the effect of ezetimibe on postprandial hyperlipidemia and hyperinsulinemia, and whether it improves endothelial function in obese metabolic syndrome (MetS)

The efficacy and safety of velagliflozin over 16\u2009weeks as a treatment for insulin dysregulation in ponies

BackgroundA previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 μIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10–12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal.ResultsVelagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 μIU/mL in wk. 0, to 119 ± 19 μIU/mL (P = 0.015) and 117 ± 15 μIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 μIU/mL in the treated group, with no rebound effect.ConclusionsVelagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.